A major objective is to understand the metabolic transformation of Steroid hormones in humans and to examine the factors which can alter these processes. Specific attempts will be made to study these factors which influence the natural history of cancer and to develop methods of treatment based on the use of hormone metabolites. We are studying pathological conditions where the steroid hormone metabolism is known to depart from normality or could be expected to do so. An immediate and long-term goal is the development of new modes of cancer treatment employing steroid metabolites. These may bypass mechanisms which operate to produce initial unresponsiveness or acquired resistance of tumors to steroid hormones. We expect to continue chemical and physiological studies essentially as they have been carried out in the past and explore the human pharmacology of steroid hormone metabolites, especially as these affect the production or transformation of endogenous hormones. The identification, chemical characterization and synthesis, where necessary, of metabolites of steroid hormones of human subjects has been, and continues to be, a central concern. These studies have embraced steroid hormones of the adrenals, gonads and placenta. The development and use of physical methods of characterization has been emphasized.